New chemicals shield 'genome guardian'

May 6 2008

Cancer Research UK scientists have discovered a potent group of chemicals that protect p53 - a major anti-tumour gene - from destruction, a study published in Cancer Cell* today (Monday) reveals.

This important discovery could potentially lead to the development of an exciting new drug for a variety of cancers. By shielding p53 from damage, the treatment could reduce tumour growth.

Known as 'the guardian of the genome', p53 is damaged or switched off in most cancers.

Researchers based in Scotland, jointly funded by Tenovus Scotland, Cancer Research UK, and the University of Dundee, have now found a family of chemicals - which could be developed into drugs in the future - that stop enzymes responsible for flagging up p53 for destruction from working.

The scientists discovered the chemicals, called tenovins, by investigating the properties of a library of 30,000 drug-like compounds.

Lead author Dr Sonia Lain, based at the University of Dundee, said: "Our findings indicate that tenovins have the potential to stop tumours. We found that tenovins work by inhibiting enzymes called sirtuins which clip off a crucial chemical group from p53, leading to its destruction.

"We hope that targeting sirtuins with drugs could treat many different cancers in the future."

The team used an innovative method to uncover tenovins, screening cells for positive reactions to thousands of chemicals.

Joint lead author, Dr Nick Westwood from the School of Chemistry at the University of St Andrews, said: "This exciting project is a great example of what can be done by researchers from different disciplines collaborating. This programme has successfully combined skills in cell and cancer biology, biochemistry, genetics and chemistry to deliver compounds of genuine therapeutic interest."

Cancer Research UK's chief scientist Professor Sir David Lane, also based at the University of Dundee, discovered the p53 protein in 1979. Since then, the p53 protein and corresponding gene has been the focus of much research. It halts the growth of damaged cells, activating DNA repair or triggering cell death.

DNA damage activates p53. Some existing cancer drugs trigger p53's anti-cancer activity by damaging DNA and activating this response. Tenovins enhance p53's activity without causing DNA damage, making them safer and more effective potential drugs.

Cancer Research UK's director of cancer information, Dr Lesley Walker, said: "We're very excited to see chemicals that could become exciting new drugs emerging from this work, which started with the discovery of p53 by Cancer Research UK in the late 70s.

"Translating the processes underlying cancer into effective treatments for patients is a major part of Cancer Research UK's strategy for beating cancer, and one which we believe will deliver many more crucial weapons in the fight against the disease.

"One of Cancer Research UK's goals is to develop treatments for many more patients that accurately target cancer and have few serious side-effects."

For media enquiries please contact the Cancer Research UK press office on 020 7061 8300 or, out-of-hours, the duty press officer on 07050 264 059.

Notes

* Discovery, in vivo activity ad mechanism of action of a small-molecule p53 activator. Sonia Lain et al. 2008. Cancer Cell.

The study was conducted in yeast, mouse and skin cancer cells.

Tenovins are named after funder Tenovus Scotland.

Cancer Research UK has developed ten goals to measure our success over the coming years in beating cancer. We will work with our partners to achieve the following by 2020:

1. People will know how to reduce their risk of cancer - Three-quarters of the UK public will be aware of the main lifestyle choices they can make to reduce their risk of getting cancer
2. The number of smokers will fall dramatically - Four million fewer adults will be smokers, preventing thousands of new cases of cancer every year
3. People under 75 will be less likely to get cancer - The chances of a person developing cancer up to the age of 75 will fall from more than one in four to one in five
4. Cancer will be diagnosed earlier - Two-thirds of all cancer cases will be diagnosed at a stage when the cancer can be successfully treated
5. We will understand how cancer starts and develops - We will have a detailed understanding of the causes and changes in the body in two-thirds of all cases of cancer
6. There will be better treatments with fewer side effects - Treatments that accurately target the cancer and have few serious side effects will be available for at least half of all patients
7. More people will survive cancer - Survival rates for all common cancers will increase, with more than two-thirds of newly-diagnosed patients living for at least five years
8. We will especially tackle cancer in low income communities - The differences in the risk of dying from cancer between the most affluent and the least affluent will be reduced by half
9. People with cancer will get the information they need - At least nine out of ten patients will be able to access the information they need at the time of diagnosis and during treatment
10. We will continue to fight cancer beyond 2020 - Sufficient scientists, doctors, nurses and infrastructure will be in place to ensure continued rapid progress in the fight against cancer beyond 2020